Advancing age is associated with an increased risk of impaired glucose tolerance and the development of type 2 diabetes. Because these disorders are themselves risk factors for diseases associated with significant morbidity and mortality, new approaches to maintain glucose homeostasis in the aged are urgently needed. Although beta cell dysfunction has been implicated as a contributing factor to disordered glucose homeostasis in the aged, the nature of the beta cell defects that emerge in older individuals has not been carefully studied. Thus, the objective of the proposed study is to identify the precise nature of the beta cell defects that emerge with age and obesity, and gain insight as to whether these defects can be mitigated by known interventions that extend healthspan.